Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats.

Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP.     

Sensitizing effects of bradykinin on the heat responses of the visceral nociceptor.

1. Whether bradykinin (BK), which is known as an endogenous pain-producing substance, induces augmentation of the discharges of polymodal receptors evoked by heat stimulation was investigated in in vitro canine testis-superior spermatic nerve preparations. 2. The heat response was significantly augmented by pretreatments with BK at concentrations greater than 0.094 nM, whereas BK induced significant increases in the mean discharge rates at concentrations above 9.4 nM. Both effects increased in a concentration-dependent manner. The augmenting effect of BK on the heat response diminished within 10 min after application of BK, regardless of concentration. 3. When 9.4 nM BK was applied in a mixture with 940 nM NPC349, a B2 receptor antagonist, the averaged mean discharge rate evoked by BK and the averaged augmenting effect were both significantly suppressed compared with those induced by BK given alone. 4. The augmenting effect of BK on the heat response of polymodal receptors could be observed even in the absence of BK-evoked discharges per se in several cases in which low concentrations of BK or BK plus B2 antagonists were given. 5. These findings suggest that the augmenting effects of BK on the heat response depend on B2 receptor-mediated intracellular processes acting in parallel to, but not directly on, the impulse-generation mechanism of the heat response of the polymodal receptor.     

EUS IN THE DIAGNOSIS OF ULCERATIVE COLITIS

The ultrasonograms of ulcerative colitis (UC) in active stage show hypoechoic changes of the colorectal wall from the mucosal layer to the deeper layers. These endoscopic ultrasound (EUS) changes of the wall recognized in active stage disappear or normalize in the stage of remission. When the stage of UC is exacerbated, the hypoechoic changes of the wall extend from the mucosal layer to the deeper layers with the increase of wall thickness. These EUS images of active UC are classified into the following types: UC‐M, thickening of the whole wall with the structure preserved; UC‐SM, hypoechoic changes reach the superficial portion of third layer with the thickening of whole wall; UC‐SM deep, hypoechoic changes reach the deeper portion of third layer with the thickening of whole wall; UC‐MP, hypoechoic changes reach the fourth layer with the thickening of whole wall; UC‐SS/SE, hypoechoic changes penetrate through the fourth layer with the thickening of whole wall. With the help of EUS we can demonstrate the severity of inflammation in UC. Moreover, in severe cases of UC, the treatment strategy including emergency surgery can be determined. EUS is a valuable method in the management of UC.     

Study on the mass-screening of after-meal serum triglyceride concentration]

The serum triglyceride concentration (TG) tested in health checks after meals cannot properly sort out hypertriglyceridemia with reference to the upper normal limit of fasting TG (150 mg/dl) set by the Japan Arteriosclerosis Society, because TG goes up considerably after a meal. In our survey of a large number of health check examinees (free of abnormal biochemical data other than TG and diseases under medical treatment), the mean (M) of fasting TG + 2 standard deviations (SD) was close to 150 mg/dl. When the screening level was set at M + 2SD for each time span after a meal, the ratio of the screened was distributed between 19.9 and 21.8%, which was close to 23.5%, the ratio of the screened on fasting. Accordingly, the nearest round number ending with zero for the first digit is suggested to be of practical use for the screening level of after-meal TG. The average TG in females was definitely lower than that of males, though proportionately increasing with age. The ratio of the screened among females aged between 20 and 49 was 5.3% on fasting and 3.2-5.8% for after-meal time spans, and that of the screened aged in their fifties was 11.3% and 8.2-12.9% respectively.     

A case report of aorto-pulmonary window associated with atrial septal defect]

The patient was a one-year-old boy, who underwent surgery with a diagnosis of atrial septal defect (ASD). During operation, aorto-pulmonary window (A-P window) which had not been detected by the preoperative examinations, was found. Therefore, the A-P window was divided prior to closing ASD. The patient is in good condition six months after the operation. The causes of the inaccurate preoperative diagnosis were discussed.     

Inhibition of inward rectifier K+ currents by angiotensin II in rat atrial myocytes: lack of effects in cells from spontaneously hypertensive rats.

We examined the effects of angiotensin II (Ang II) on inward rectifier K+ currents (IK1) in rat atrial myocytes. [125I]Ang II-binding assays revealed the presence of both Ang II type 1 (AT1) and type 2 (AT2) receptors in atrial membrane preparations. Ang II inhibited IK1 in isolated atrial myocytes with an IC50 of 46 nmol/l. This inhibition was abolished by the AT, antagonist RNH6270 but not at all by the AT2 antagonist PD123319. Treatment of cells with pertussis toxin or a synthetic decapeptide corresponding to the carboxyl-terminus of Gialpha-3 abolished the inhibition by Ang II, indicating the role of a Gi-dependent signaling pathway. Accordingly, Ang II failed to inhibit IK1 in the presence of forskolin, dibutyryl-cAMP or protein kinase A catalytic subunits. In spite of the increased binding capacities for [125I]Ang II, Ang II failed to affect IKI in cells from spontaneously hypertensive rats (SHR). AT, immunoprecipitation from atrial extracts revealed decreased amounts of Gialpha-2 and Gialpha-3 proteins associated with this receptor in SHR as compared with controls. The reduced coupling of AT, with Gialpha. proteins may underlie the unresponsiveness of atrial IK1 to Ang II in SHR cells.     

NEWLY DEVELOPED ULTRASOUND ENDOSCOPE WITH AN ELECTRONIC RADIAL ARRAY TRANSDUCER

A prototype electronic radial scan ultrasound endoscope has been developed by Olympus (Tokyo, Japan) for endoscopic ultrasound (EUS) study. The ultrasound view‐angle of this model is 360° vertical to the scope. Though the diameter of the scanner and the shaft of the scope is bigger than those of the present mechanical radial scan model, clinical manipulation of the new scope is the same as that of the present model. Image quality of the ultrasound picture demonstrated by the electronic radial model was as clear as those provided by the mechanical radial scan model. Ultrasound penetration was better and satisfactory because of less echoic reduction compared to the mechanical radial model. The newly developed electronic radial model can be evaluated as an ultrasound endoscope for the next generation. The advantage of this system is to facilitate the clinical use of color Doppler function and tissue harmonic imaging, and this system can be operated by the same monitor unit as a convex model of ultrasound endoscope.